Alpha interferon comprises a family of leukocyte-derived cytokines that exhibit antiviral, antiproliferative and immunomodulatory effects on many cell types. Recombinant human alpha-interferon is used to treat a variety of viral diseases and cancers and had worldwide sales in excess of $1.4 billion during 1997. We propose to create modified alpha-interferon proteins that are equal or superior to natural alpha-interferon at modulating immune responses and viral and cell proliferation in vivo, but which require less frequent dosing, on the order of once per week to once per month, rather than daily. During Phase I identified sites in alpha-interferon that can be modified without affecting the protein's in vitro bioactivity. During Phase II, we will develop manufacturing processes to produce sufficient quantities of the modified alpha-interferon proteins for testing in animal models of cancer and viral diseases. The improved characteristics of the novel alpha-interferon proteins should reduce the amount of alpha- interferon required per patient, reduce toxicity, improve parent compliance and quality of life and result in considerable cost savings to patients and healthcare providers. Alpha-interferons are members of a large family of structurally related growth factors and cytokines. Information gained from these studies will aid in creating long-acting versions of other members of this gene family for use in treating cancer, infectious disease and hematopoeitic disorders. PROPOSED COMMERCIAL APPLICATION: Recombinant human alpha-interferon is used to treat a variety of viral diseases and cancers and had worldwide sales in excess of $ 1.4 billion in 1997. The modified alpha-interferon proteins under development will require much less frequent dosing than existing alpha-interferon products, resulting in significant cost savings to patients and healthcare providers. Additional benefits may include improved drug efficacy, reduced toxicity and improved patient quality of life.